Febuxostat, 2-(3-cyano-4-isobutyloxy-phenyl)-4-methyl-5-thiazolecarboxylic acid regulates the biosynthesis of uric acid in vivo and is indicated for the use in the treatment of hyperuricemia and gout. It received marketing approval in EU (brand name Adenuric) and US (brand name Uloric) and is represented by the following general formula (I):

Specific crystal forms of Febuxostat designated as forms A, B, C, D and G are disclosed for example in EP 1020454.
Polymorphism is a phenomenon relating to the occurrence of different crystal forms for one molecule. There may be several different crystalline forms for the same molecule with distinct crystal structures and varying in physical properties like melting point. XRPD spectrum and IR-spectrum. These polymorphs are thus distinct solid forms which share the molecular formula of the compound from which the crystals are made up, however they may have distinct advantageous physical properties which can have a direct effect on the ability to process and/or manufacture the drug substance, like flowability, and the drug product, like flowability, as well as on drug product stability, dissolution, and bioavailability.
These distinct physical properties of different polymorphs of the same compound can render different polymorphs more, or less, useful for a particular purpose, such as for pharmaceutical formulation.
The crystal forms of Febuxostat disclosed for example in EP1020454, namely anhydrate A, anhydrate B, anhydrate C, hydrate G and a solvate with methanol (Form D) have certain drawbacks. The drawbacks of forms other than form A are explained in U.S. Pat. No. 7,361,676.
U.S. Pat. No. 7,361,676 discloses formulations comprising form A. In the comparative examples of said patent the drawbacks using known forms of Febuxostat others than form A are presented and explained in detail. The problems encountered with the non-A forms are, for example, polymorph conversion during formulation or stability studies resulting in non uniform dissolution. Polymorph A according to both references above is therefore the preferred solid state form of Febuxostat intended for formulation, however the solubility of form A is limited, as it has a value of 0.22 mg/ml.
Moreover, the preferred form A is difficult to make as form A is said to be obtainable in pure form only in a quite narrow window of temperature and methanol/water ratio in the region I as shown in FIG. 1 of EP1020454. The process to obtain pure form A is especially critical, as different polymorphic forms of Febuxostat are obtainable from the same solvent system.
Crystal forms of Febuxostat with both higher solubility and fewer problems with regard to polymorphic conversion during preparation and/or typical formulation conditions would facilitate the production of pharmaceutical compositions while at the same time more efficiently provide Febuxostat to a patient in need thereof. There is thus a need for solid forms of Febuxostat which avoid one or more problems of the known crystal forms.